Importin: Difference between revisions

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New page: <StructureSection load='1ee5' size='340' side='right' caption='Structure of yeast importin α NLS-binding domain complex with nucleoplasmin peptide (PDB code 1ee5).' scene=''> == Fun...
 
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<StructureSection load='1ee5' size='340' side='right' caption='Structure of yeast importin α NLS-binding domain (grey) complex with nucleoplasmin peptide (green) (PDB code [[1ee5]]).' scene=''>


<StructureSection load='1ee5' size='340' side='right' caption='Structure of yeast importin α NLS-binding domain complex with nucleoplasmin peptide (PDB code [[1ee5]]).' scene=''>
== Function ==


== Function ==
'''Importins''' (IPO) mediate the import of cellular proteins into the nucleus by binding to the '''N'''uclear '''L'''ocalization '''S'''ignal (NLS).  IPO has 2 subunits: α and β.  '''IPO-α''' is an adaptor protein which binds the NLS<ref>PMID:9759490</ref>.  IPOs can contain one or two NLS motifs. 
*'''IPO-α''' contains several armadillo repeats with two NLS-binding sites and an IPO-β binding (IBB) site. 
*'''IPO-β''' contains 19 HEAT (solenoid domain) repeats.  Many nuclear proteins contain Phe-Gly sequences which can bind to HEAT repeats and thus be transported. 
*'''IPO-4''' binds histones H3 and H4 and histone chaperone ASF1 for nuclear import<ref>PMID:36103578</ref>. 
*'''IPO-7'''  drives the nuclear import of the regulator of mechanotransduction pathway YAP<ref>PMID:35246520</ref>.
*'''IPO-9''' binds histones H2A and H2B for nuclear import<ref>PMID:30855230</ref>.
*'''IPO-13''' has a role in oxidative stress-dependent nuclear export<ref>PMID:34625540</ref>.


'''Importins''' (IPO) mediate the import of cellular proteins into the nucleus by binding to the nuclear localization signal (NLS).  IMP has 2 subunits: α and β.  IPO-α is an adaptor protein which binds the NLS.  Proteins can contain one or two NLS motifs.  IPO-α contains several armadillo repeats with two NLS-binding sites and an IPO-β binding site (IBB).  IPO-β contains 19 HEAT repeats.  Many nuclear proteins contain Phe-Gly sequences which can bind to HEAT repeats and thus be transported.
See also [[Protein Transport Membrane Protein]].


== Disease ==
== Disease ==
IPO-α isoform expression is altered in many kinds of cancer. 


== Relevance ==
== Relevance ==
Specific IPO-α isoforms  are critical in nerve regenerative response after injury.  Loss of IPO-α expression in aging myocardial cells could make recovery after heart disease in elderly patients more difficult<ref>PMID:25656054</ref>.


== Structural highlights ==
== Structural highlights ==


==3D structures of importin==
==3D structures of importin==
[[Importin 3D structures]]


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
</StructureSection>
 
'''IPO-α'''
 
[[1ial]] – mIPO residues 44-496 – mouse<br />
[[1bk5]] – yIPO NLS-binding domain - yeast<br />
 
''IPO-α complex with NLS peptide''
 
[[1ejl]] – mIPO NLS-binding domain + SV40 large T antigen<br />
[[1ejy]] – mIPO NLS-binding domain + nucleoplasmin <br />
[[2ynr]] – mIPO NLS-binding domain + B54NLS <br />
[[1bk6]] – yIPO NLS-binding domain + SV40 large T antigen<br />
[[1ee4]] – yIPO NLS-binding domain (mutant) + c-Myc<br />
[[1ee5]] – yIPO NLS-binding domain (mutant) + nucleoplasmin<br />
[[1un0]], [[2c1t]] – yIPO NLS-binding domain (mutant) + Nup2<br />
 
''IPO-α complex with protein''
 
[[1wa5]] – yIPO NLS-binding domain + GTPase Ran + IPO-α re-exporter<br />
 
'''IPO-α 1'''
 
''IPO-α 1 complex with NLS peptide''
 
[[4mz5]], [[4mz6]] – mIPO NLS-binding domain + dUTPase<br />
[[4oih]] – mIPO NLS-binding domain + guanine nucleotide exchange factor SRM1<br />
 
''IPO-α 1 complex with protein''
 
[[2jdq]] – hIPO NLS-binding domain + polymerase basic protein  2 C terminal<br />
[[3tj3]] – hIPO NLS-binding domain + Nup50 N terminal<br />
[[2jdq]] – hIPO NLS-binding domain + telomerase reverse transcriptase peptide<br />
 
'''IPO-α 2'''
 
[[3tpo]] – mIPO<br />
[[1iq1]] – mIPO NLS-binding + autoinhibitory peptide domains<br />
[[4e4v]] – hIPO NLS-binding domain (mutant) - human <br />
 
''IPO-α 2 complex with NLS peptide''
 
[[1pjm]] – mIPO NLS-binding domain + retinoblastoma-associated protein<br />
[[1pjn]] – mIPO NLS-binding domain + histone-binding protein N1/N2<br />
[[1q1s]], [[1q1t]] – mIPO NLS-binding domain + SV40 large T antigen<br />
[[1y2a]], [[3q5u]] – mIPO NLS-binding domain + phospholipid scramblase <br />
[[2c1m]] – mIPO NLS-binding domain + Nup50<br />
[[3btr]] – mIPO NLS-binding domain + androgen receptor<br />
[[3knd]] – mIPO NLS-binding domain + targeting protein for KXLP2<br />
[[3l3q]] – mIPO NLS-binding domain + library peptide<br />
[[3oqs]] – mIPO NLS-binding domain + CLIC4<br />
[[3rz9]] – mIPO NLS-binding domain + KU80<br />
[[3rzx]] – mIPO NLS-binding domain + KU70<br />
[[3tpm]] – mIPO NLS-binding domain + MAL<br />
[[3ve6]] – mIPO NLS-binding domain + Venezuelan equine encephalitis virus<br />
[[3uvu]] – mIPO NLS-binding domain + flap endonuclease<br />
[[3ukw]], [[3ukx]] – mIPO NLS-binding domain + BIMAX<br />
[[3uky]], [[3ukz]], [[3ul0]] – mIPO NLS-binding domain + nuclear CAP-binding protein<br />
[[3ul1]] – mIPO NLS-binding domain + nucleoplasmin <br />
[[4htv]] – mIPO NLS-binding domain + capsid protein <br />
[[4ba3]] – mIPO NLS-binding domain + A89NLS <br />
[[3zio]], [[3zip]], [[3ziq]], [[3zir]] – mIPO NLS-binding domain + minor site-specific NLS <br />
[[3zin]] – mIPO NLS-binding domain + nucleolar RNA helicase<br />
 
''IPO-α 2 complex with protein''
 
[[3fex]], [[3fey]] – mIPO NLS-binding domain + nuclear CAP-binding protein<br />
 
'''IPO-β 1'''
 
[[3nd2]] – yIPO <br />
[[1gcj]] – mIPO N terminal<br />
 
''IPO-β 1 complex with protein''
 
[[1qgx]], [[1qgr]] – hIPO + IPO-α 2 IBB domain<br />
[[1ibr]] – hIPO + GTPase Ran<br />
[[2bku]], [[3ea5]] – yIPO + GTPase Ran<br />
[[1f59]], [[1o6p]], [[1o6o]] – hIPO + FXFG nucleoporin repeats<br />
[[1m5n]] – hIPO HEAT repeats 1-11 + parathyroid hormone-related protein NLS peptide<br />
[[2p8q]], [[2q5d]], [[2qna]], [[3lww]] – hIPO + RNA U transporter N terminal<br />
[[1qgr]], [[3w5k]] – hIPO + zinc finger protein SNAI1<br />
[[2bpt]] – yIPO + Nup1<br />
[[1ukl]] – mIPO + SREBP-2<br />
 
'''IPO-β 2 (Transportin 1)'''
 
[[2z5j]], [[2qmr]] – hIPO <br />
 
''IPO-β 2 complex with protein''
 
[[2h4m]], [[2ot8]], [[2z5n]] – hIPO + hnRNP peptide<br />
[[2z5k]], [[2z5m]] – hIPO + nuclear RNA export factor peptide<br />
[[2z5o]] – hIPO + JKTBP peptide<br />
[[4fdd]], [[4jlq]], [[4oo6]] – hIPO + RNA binding protein peptide<br />
[[4fq3]] – hIPO + FUS peptide<br />
 
'''IPO-13'''
 
[[2x19]] – hIPO + GTPase Ran<br />
[[2xwu]] – hIPO + UBC9<br />
[[3zjy]] – hIPO + GTPase Ran + EIF-1A<br />
 


== References ==
== References ==